In order to understand the mechanism of antitumor effects, we are investigating the role of cytokines in the regulation of immunity in vitro and in vivo. Interferon-alpha (IFN-alpha), IL-2, IL-6 and other cytokines are investigated. Our initial paper in which we demonstrated that IFN- alpha synergized with IL-2 in the augmentation of lymphokine activated killer (LAK) cells in various compartments of mice is in press. Both proliferation and augmentation of LAK cell activity on a per cell basis was observed in response to IFN-alpha and IL-2 therapy. Our observations suggest that anti-tumor effects of IFN-alpha with IL-2 may be mediated by the activation of LAK cells. It is of interest that the administration of IFN-gamma with IL-2 caused increased LAK activity while it has not been shown to cause synergistic anti-tumor effects. Other effectors such as CTL, macrophages and unknown population may be responsible for the differences observed with the two interferons. Currently, CTL response after IL-2 and IFN-alpha or IFN-gamma administration and augmentation of LAK activity in response to IFN-alpha and gamma alone are being examined. We are also examining the immune regulatory effects of IL-6 in vivo. This project is still active.